HCV, which is found in all parts of the world, has been characterized as single-stranded RNA virus of about 9.5 kilobases in length. Choo et al., Science, 244: 395-62 (1989).
Surgery patients and others requiring blood transfusions, and especially those having suppressed immune systems, resulting, for example, from drugs administered in connection with organ transplantation, are at risk of developing HCV infection, which is the primary cause of transfusion-associated hepatitis in the world today. It has been estimated that posttransfusion hepatitis C may be responsible for up to 3,000 annual cases of chronic active hepatitis or cirrhosis of the liver in the U.S. alone. Hemodialysis patients, as well as intravenous drug abusers are other groups which are at risk for acquiring HCV infection.
The mechanism by which HCV replicates has not been thoroughly elucidated, thus hindering research aimed at developing an effective vaccine. Immune globulin has been reported for prophylaxis of transfusion-associated viral hepatitis. However, the Centers for Disease Control do not presently recommend immune globulin for this purpose.
Various clinical studies have been conducted with the goal of identifying pharmaceutical agents capable of effectively treating HCV infection in patients afflicted with chronic hepatitis C. These studies have involved the use of dideoxynucleoside analogues and interferon-alpha, alone and in combination therapy with other anti-viral substances. Such studies have shown, however, that substantial numbers of the participants do not respond to this therapy, and of those that do respond favorably, a large proportion were found to relapse after termination of treatment.
Thus, a need exists for new anti-viral agents and treatments for HCV infection that overcome the limitations of existing pharmaceutical therapies. Insofar as is known, heterocyclic-substituted carboxamides and analogues thereof have not been previously reported as being useful for the treatment of HCV.